Novel Mechanism Underlies Aldosterone-Induced Heath Damage

When the heart begins to fail, the body does everything in its power to fix the situation. But sometimes, those compensatory mechanisms ultimately do more harm than good. Such is the case with the adrenal hormone aldosterone, which stimulates the heart to pump harder, causing greater damage to the heart muscle. But now, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) are closer than ever to putting the brakes on that process. With their recent discovery of an unexpected mechanism by which signaling molecules known as G protein-coupled receptor kinases (GRKs) mediate aldosterone-induced heart damage, they have opened the path to an important therapeutic advance. "It turns out that two kinases, GRK2 and GRK5, contribute to the pathology of heart failure by inducing specific changes in myocytes (heart cells) down-stream of mineralocorticoid receptors that bind aldosterone," explained Dr. Walter J. Koch (photo), Ph.D., William Wikoff Smith Endowed Chair in Cardiovascular Medicine, Professor and Chair of the Department of Pharmacology, Director of the Center for Translational Medicine at LKSOM and senior investigator on the new study. The report, published online on March 2, 2016 in the journal Nature Communications, is the first to shed light on the unique interaction. The open-access article is titled “Myocardial Pathology Induced by Aldosterone Is Dependent on Non-Canonical Activities of G Protein-Coupled Receptor Kinases.”"When aldosterone binds to its receptor, GRK2 moves to the mitochondria, where it stimulates pro-death pathways, and GRK5 moves to the cell nucleus, where it activates pathways that cause heart cells to grow, making them less efficient," Dr. Koch said.
Login Or Register To Read Full Story